Bone morphogenetic proteins (BMPs) are the family of proteins isolated from demineralized bone and known to be able to induce ectopic bone formation. As such, BMP is of value as a bone formation promoting agent for bone fracture healing and bone remodeling [A. E. Wang, Trends Biotechnol., 11, 379-383, 1993].
Furthermore, since it directly promotes osteoblast differentiation, BMP is supposed to be playing the role of a coupling factor in bone remodeling and is, therefore, considered to be closely associated with bone metabolism. It has also been reported that the BMP content of bone matrix in aged animals has been considerably depressed [M. L. Urist, Bone and Mineral Research, 6 (ed by W. A. Peck), 57-112, Elsevier, 1989], indicating that BMP is closely related to the maintenance of bone mass. This finding suggests that BMP may be a promising drug for the treatment of various diseases of bone, such as osteoporosis. However, BMP usually exists only in trace amounts in the organisms, and sources of its supply were limited. Moreover, as it is a protein, the routes of administration are restricted, and therefore the spectrum of diseases which can be treated is quite limited.
It has also been reported that BMP has neurotrophic factor-like activity [V. M. Paralkar et al., J. Cell Biol., 119, 1721-1728, 1992]. Also known is an intense expression of the BMP gene in the brain tissue [E. Ozkaynak et al., Biochem. Biophys. Res. Commun., 179, 116-123, 1991]. It has also been suggested that BMP is playing an important role in the formation of the neural tube during embryonic development [K. Basler et al., Cell, 73, 687-702, 1993]. It is, therefore, believed that BMP is closely involved in the differentiation or functional maintenance of nerve cells.
Neurotrophic factor (NTF) is a family of proteins playing important roles in the maintenance of neuron and functional expression of neurons and includes nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and glial cell line-derived neurotrophin factor (GDNF), among others. NGF in the peripheral nervous system promotes the differentiation and maturation of the neural crest sympathetic ganglion and dorsal root ganglion cells [A. M. Davies & R. M. Lindsay, Dev. Biol., 111, 62-72, 1985; R. Levi-Montalcini, EMBO J., 6, 1145-1154, 1987] and in the central nervous system acts on the cholinergic neurons of septa (forebrain basal ganglia) [H. Gnahn et al, Dev. Brain Res., 9, 45-52, 1983; H. Hatanaka & H. Tsukui, Dev. Brain Res., 30, 47-56, 1986; F. Hefti, J. Neurosci., 6, 2155-2162, 1986]. NGF is necessary for the maintenance of nerve function even after completion of differentiation of neurons. BDNF in the peripheral nervous system acts on the dorsal root ganglion and nodular ganglion cells but does not act on sympathetic ganglion cells [R. M. Lindsay & H. Rohrer, Dev. Biol., 112, 30-48, 1985; R. M. Lindsay et al., Dev. Biol., 112, 319-328, 1985; A. M. Davies et al., J. Neurosci., 6, 1897-1904, 1986]. In the central nervous system, BDNF acts on the cholinergic neurons and GABA (.gamma.-aminobutyric acid)-nergic neurons of septa and the dopaminergic neurons of midbrain [R. F. Alderson et al., Neuron, 5, 297-306, 1990; C. Hyman et al., Nature, 350, 230-232, 1991; B. Knusel et al., Proc. Natl. Acad. Sci. USA, 88, 961-965, 1991]. The activites of NT-3 on the peripheral nervous system are similar to that of NGF and BDNF, however NT-3 characteristically acts strongly on neural placodes-derived sensory neurons [P. Ernfors et al., Proc. Natl. Acad. Sci. USA, 87, 5454-5458, 1990; A. Rosenthal et al., Neuron, 4, 767-773, 1990]. In the central nervous system, however, there is not known a nerve cell responsive to NT-3.
GDNF promotes the survival and morphelogical differentiation of dopaminergic neurons and increases their high affinity dopamine uptake [L-F. H. Lin et al., Science, 260, 1130-1132 (1993)].
In Alzheimer type dementia, the degeneration and exfoliation of cholinergic neurons of the forebrain basal ganglia inclusive of septa and an extensive lesion and exfoliation of cerebrocortical neurons have been observed. The NGF and neurotrophic factors discovered more recently are considered among candidate therapeutic drugs for this disease [F. Hefti & W. J. Weiner, Annu. Neurol., 20, 275-281, 1986]. Furthermore, in Parkinson's disease which is a syndrome involving the degeneration and exfoliation of dopaminergic neurons of midbrain, BDNF and GDNF as neurotrophic factors for the associated neurons have been considered to be a promising therapeutic drugs. However, since those neurotrophic factors are proteins,. their applicability is limited.
As compounds in the lactone series which are of use as synthetic intermediates for the fused cyclic compound [I] of the present invention, the following compounds have been disclosed.
(1) Helioxanthin, which has the following formula ##STR1## [R. S. Burden et al., J. Chem. Soc. (C), 693-701, 1969](2) Compounds of the following formulas ##STR2## [Arch. Pharmacol., 328 (9), 640-644, 1995](3) Compounds of the following formulas ##STR3## [Indian J. Chem., Sect. B: Org. Chem. Include. Med. Chem., 33B (9), 839-846, 1994] PA1 (4) Compounds of the following formulas ##STR4## [Indian J. Chem. Sect. B: 31B (7), 401-406, 1992](5) Compounds of the following formulas ##STR5## [Chem. Pharm. Bull., 32 (1), 31-7, 1984](6) Compounds of the following formulas ##STR6## [J. Chem. Soc. B, (11), 2091-2094, 1971](7) Compounds of the following formula ##STR7## [Phytochemistry, 29 (9), 2991-2993, 1990](8) Compounds of the following formulas ##STR8## [Journal of Natural Products, 43 (4), 482-486, 1980](9) A compound of the following formula ##STR9## [J. Chem. Soc. C, (5), 693-701, 1969] PA1 Y is an optionally substituted methylene group, S(O)q wherein q is an integer of 0 to 2, or an optionally substituted imino group; PA1 Z.sup.1 is a C.sub.1-3 alkylene group which may have an oxo group or a thioxo group; PA1 Z.sup.2 is an optionally substituted C.sub.1-3 alkylene group; PA1 Ar is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group; PA1 one of R.sup.1 and R.sup.2 is a hydrogen atom, a halogen atom, a hydroxyl group, an optionally substituted lower alkyl group, or an optionally substituted lower alkoxy group; PA1 the other is a halogen atom, a hydroxyl group, an optionally substituted lower alkyl group, or an optionally substituted lower alkoxy group; or PA1 R.sup.1 and R.sup.2 taken together with adjacent --c.dbd.c-- form a ring; and PA1 ring A is a benzene ring which may have a substituent in addition to R.sup.1 and R.sup.2 ; or a salt thereof. The inventors further found that the above compound [I] and its salt have unexpectedly high BMP-like activity, neurotrophic factor-like activity or the corresponding enhancing activity and are well qualified as medicines. The present invention has been developed on the basis of the above finding. PA1 1. A compound of the formula: ##STR11## wherein Q is an optionally substituted carbon atom or N(O)p wherein p is 0 or 1; PA1 Y is an optionally substituted methylene group, S(O)q wherein q is an integer of 0 to 2, or an optionally substituted imino group; PA1 Z.sup.1 is a C.sub.1-3 alkylene group which may have an oxo group or a thioxo group and may contain etherified oxygen or sulfur within the carbon chain; PA1 Z.sup.2 is an optionally substituted C.sub.1-3 alkylene group; PA1 Ar is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group; PA1 one of R.sup.1 and R.sup.2 is a hydrogen atom, a halogen atom, a hydroxyl group, an optionally substituted lower alkyl group, or an optionally substituted lower alkoxy group; PA1 the other is a halogen atom, a hydroxyl group, an optionally substituted lower alkyl group, or an optionally substituted lower alkoxy group; or PA1 R.sup.1 and R.sup.2 taken together with adjacent --c.dbd.c-- form a ring; and PA1 ring A is a benzene ring which may be substituted in addition to R.sup.1 and R.sup.2 ; or a salt thereof, PA1 2. A compound as described in the above item 1, wherein PA1 Q is (A) CR.sup.4 wherein R.sup.4 is (1) a hydrogen atom, (2) a halogen atom, (3) a C.sub.1-16 acyclic or cyclic hydrocarbon group which may have 1 to 5 substituents selected from the group consisting of (i) a halogen, (ii) a C.sub.1-3 alkylenedioxy, (iii) a nitro, (iv) a cyano, (v) a C.sub.1-6 alkyl optionally having 1 to 3 halogen atoms, (vi) a C.sub.3-6 cycloalkyl, (vii) a C.sub.1-6 alkoxy which may be substituted with amino, mono- or di-C.sub.1-6 alkylamino or C.sub.1-6 alkoxycarbonyl, and optionally having 1 to 3 halogen atoms, (viii) a C.sub.1-6 alkylthio optionally having 1 to 3 halogen atoms, (ix) a hydroxyl, (x) an amino, (xi) a mono-C.sub.1-6 alkylamino, (xii) a di-C.sub.1-6 alkylamino, (xiii) a C.sub.1-6 alkyl-carbonyl, (xiv) a C.sub.1-6 alkyl-carbonyloxy, (xv) a C.sub.1-6 alkyl-carbonyloxy-C.sub.1-3 alkyl, (xvi) a carboxyl, (xvii) a C.sub.1-6 alkoxy-carbonyl, (xviii) a mono-C.sub.1-6 alkylamino-carbonyl, (xix) a di-C.sub.1-6 alkylamino-carbonyl, (xx) a carbamoyl, (xxi) a mono-C.sub.1-6 alkyl-carbamoyl, (xxii) a di-C.sub.1-6 alkyl-carbamoyl, (xxiii) a sulfo, (xxiv) a C.sub.1-6 alkylsulfonyl, (xxv) a C.sub.6-10 aryl, (xxvi) a C.sub.6-10 aryloxy, (xxvii) a 5- to 7-membered heterocyclic group having 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur in addition to carbon atoms, said heterocyclic group being optionally fused with a benzene ring, (xxviii) thiocarbamoyl, (xxix) mono-C.sub.1-6 alkylthio-carbamoyl, (xxx) di-C.sub.1-6 alkylthio-carbamoyl, (xxxi) C.sub.6-10 aryl-carbamoyl and (xxxii) C.sub.6-10 aryl-thiocarbamoyl, or (4) a hydroxyl group which may be substituted with a C.sub.1-16 acyclic or cyclic hydrocarbon group which may have 1 to 5 substituents selected from the group consisting of (i) a halogen, (ii) a C.sub.1-3 alkylenedioxy, (iii) a nitro, (iv) a cyano, (v) a C.sub.1-6 alkyl optionally having 1 to 3 halogen atoms, (vi) a C.sub.3-6 cycloalkyl, (vii) a C.sub.1-6 alkoxy which may be substituted with amino, mono- or di-C.sub.1-6 alkylamino or C.sub.1-6 alkoxycarbonyl, and optionally having 1 to 3 halogen atoms, (viii) a C.sub.1-6 alkylthio optionally having 1 to 3 halogen atoms, (ix) a hydroxyl, (x) an amino, (xi) a mono-C.sub.1-6 alkylamino, (xii) a di-C.sub.1-6 alkylamino, (xiii) a C.sub.1-6 alkyl-carbonyl, (xiv) a C.sub.1-6 alkyl-carbonyloxy, (xv) a C.sub.1-6 alkyl-carbonyloxy-C-.sub.1-3 alkyl, (xvi) a carboxyl, (xvii) a C.sub.1-6 alkoxy-carbonyl, (xviii) a mono-C.sub.1-6 alkylamino-carbonyl, (xix) a di-C.sub.1-6 alkylamino-carbonyl, (xx) a carbamoyl, (xxi) a mono-C.sub.1-6 alkyl-carbamoyl, (xxii) a di-C.sub.1-6 alkyl-carbamoyl, (xxiii) a sulfo, (xxiv) a C.sub.1-6 alkylsulfonyl, (xxv) a C.sub.6-10 aryl, (xxvi) a C.sub.6-10 aryloxy, (xxvii) a 5- to 7-membered heterocyclic group having 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur in addition to carbon atoms, said heterocyclic group being optionally fused with a benzene ring, (xxviii) thiocarbamoyl, (xxix) mono-C.sub.1-6 alkylthio-carbamoyl, (xxx) di-C.sub.1-6 alkylthio-carbamoyl, (xxxi) C.sub.6-10 aryl-carbamoyl and (xxxii):C.sub.6-10 aryl-thiocarbamoyl; PA1 or (B) N(O)p wherein p is 0 or 1; PA1 Y is (1) a group of the formula: ##STR12## wherein R.sup.9 and R.sup.9' may be the same or different and each is (i) a hydrogen, (ii) a C.sub.1-6 alkyl which may be substituted with amino, mono- or di-C.sub.1-6 alkylamino or C.sub.1-6 alkoxycarbonyl, and optionally having 1 to 3 halogen atoms, (iii) a C.sub.1-6 alkoxy optionally having 1 to 3 halogen atoms, (iv) a C.sub.1-6 alkylthio optionally having 1 to 3 halogen atoms, (v) a hydroxyl, (vi) a cyano, (vii) a C.sub.1-6 alkyl-carbonyl, (viii) a C.sub.1-6 alkyl-carbonyloxy, (ix) a formylamino, (x) an amino, (xi) a mono-C.sub.1-6 alkylamino, (xii) a di-C.sub.1-6 alkylamino, (xiii) a carboxyl, (xiv) a C.sub.1-6 alkoxy-carbonyl, or (xv) a C.sub.1-6 alkyl-carbonylamino; PA1 Z.sup.1 is a C.sub.1-3 alkylene group which may have an oxo or thioxo group; PA1 Z.sup.2 is a C.sub.1-3 alkylene group which may contain oxygen or sulfur within the carbon chain as an ether or thioether and may have a substituent selected from the group consisting of (a) a halogen, (b) a C.sub.1-3 alkylenedioxy, (c) a nitro, (d) a cyano, (e) a C.sub.1-6 alkyl optionally having 1 to 3 halogen atoms, (f) a C.sub.3-6 cycloalkyl, (g) a C.sub.1-6 alkoxy which may be substituted with amino, mono- or di-C.sub.1-6 alkylamino or C.sub.1-6 alkoxycarbonyl, and optionally having 1 to 3 halogen atoms, (h) a C.sub.1-6 alkylthio optionally having 1 to 3 halogen atoms, (i) a hydroxyl, (j) an amino, (k) a mono-C.sub.1-6 alkylamino, (l) a di-C.sub.1-6 alkylamino, (m) a C.sub.1-6 alkyl-carbonyl, (n) a C.sub.1-6 alkyl-carbonyloxy, (o) a C.sub.1-6 alkyl-carbonyloxy-C.sub.1-3 alkyl, (p) a carboxyl, (q) a C.sub.1-6 alkoxy-carbonyl, (r) a mono-C.sub.1-6 alkylamino-carbonyl, (s) a di-C.sub.1-6 alkylamino-carbonyl, (t) a carbamoyl, (u) a mono-C.sub.1-6 alkyl-carbamoyl, (v) a di-C.sub.1-6 alkyl-carbamoyl, (w) a sulfo, (x) a C.sub.1-6 alkylsulfonyl, (y) a C.sub.6-10 aryl, (z) a C.sub.6-10 aryloxy, (aa) a 5- to 7-membered heterocyclic group having 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur in addition to carbon atoms, said heterocyclic group being optionally fused with a benzene ring, (bb) thiocarbamoyl, (cc) mono-C.sub.1-6 alkylthio-carbamoyl, (dd) di-C.sub.1-6 alkylthio-carbamoyl, (ee) C.sub.6-10 aryl-carbamoyl and (ff) C.sub.6-10 aryl-thiocarbamoyl; PA1 Ar is (1) a 3- to 14- membered monocyclic or fused polycyclic nonaromatic hydrocarbon group which may have 1 to 5 substituents selected from the group consisting of (i) a halogen, (ii) a C.sub.1-3 alkylenedioxy, (iii) a nitro, (iv) a cyano, (v) a C.sub.1-6 alkyl optionally having 1 to 3 halogen atoms, (vi) a C.sub.2-6 alkenyl optionally having 1 to 3 halogen atoms, (vii) a C.sub.2-6 alkynyl optionally having 1 to 3 halogen atoms, (viii) a C.sub.3-6 cycloalkyl, (ix) a C.sub.1-6 alkoxy which may be substituted with amino, mono- or di-C.sub.1-6 alkylamino or C.sub.1-6 alkoxycarbonyl, and optionally having 1 to 3 halogen atoms, (x) a C.sub.1-6 alkylthio optionally having 1 to 3 halogen atoms, (xi) a hydroxyl, (xii) an amino, (xiii) a mono-C.sub.1-6 alkylamino, (xiv) a di-C.sub.1-6 alkylamino, (xv) 5- or 6- membered cyclic amino, (xvi) --NHCOOR.sup.6 wherein R.sup.6 is as defined above, (xvii) --NHCONHR.sup.6 wherein R.sup.6 is as defined above, (xviii) --NHCOR.sup.6 wherein R.sup.6 is as defined above, (xix) --NHSO.sub.2 R.sup.6 wherein R.sup.6 is as defined above, (xx) a C.sub.1-6 alkyl-carbonyl, (xxi) a carboxyl, (xxii) a C.sub.1-6 alkoxy-carbonyl, (xxiii) a carbamoyl, (xxiv) a mono-C.sub.1-6 alkyl-carbamoyl, (xxv) a di-C.sub.1-6 alkyl-carbamoyl, (xxvi) a C.sub.6-10 aryl-carbamoyl, (xxvii) a sulfo, (xxviii) a C.sub.1-6 alkylsulfonyl, (xxvix) a C.sub.6-10 aryl, (xxx) a C.sub.6-10 aryloxy, (xxxi) C.sub.7-16 aralkyloxy, (xxxii) thiocarbamoyl, (xxxiii) mono-C.sub.1-6 alkylthio-carbamoyl, (xxxiv) di-C.sub.1-6 alkylthio-carbamoyl, (xxxv) C.sub.6-10 aryl-carbamoyl and (xxxvi) C.sub.6-10 aryl-thiocarbamoyl, PA1 R.sup.1 and R.sup.2 taken together, to form the ring with adjacent --C.dbd.C--, are (l) a C.sub.1-6 alkylene group which may have 1 to 5 Substituents selected from the group consisting of (a) a halogen, (b) a C.sub.1-3 alkylenedioxy, (c) a nitro, (d) a cyano, (e) a C.sub.1-6 alkyl optionally which may be substituted with amino, mono- or di-C.sub.1-6 alkylamino or C.sub.1-6 alkoxycarbonyl, and having 1 to 3 halogen atoms, (f) a C.sub.3-6 cycloalkyl, (g) a C.sub.1-6 alkoxy optionally having 1 to 3 halogen atoms, (h) a C.sub.1-6 alkylthio optionally having 1 to 3 halogen atoms, (i) a hydroxyl, (j) an amino, (k) a mono-C.sub.1-6 alkylamino, (l) a di-C.sub.1-6 alkylamino, (m) a C.sub.1-6 alkyl-carbonyl, (n) a C.sub.1-6 alkyl-carbonyloxy, (o) a C.sub.1-6 alkyl-carbonyloxy-C.sub.1-3 alkyl, (p) a carboxyl, (q) a C.sub.1-6 alkoxy-carbonyl, (r) a mono-C.sub.1-6 alkylamino-carbonyl, (s) a di-C.sub.1-6 alkylamino-carbonyl, (t) a carbamoyl, (u) a mono-C.sub.1-6 alkyl-carbamoyl, (v) a di-C.sub.1-6 alkyl-carbamoyl, (w) a sulfo, (x) a C.sub.1-6 alkylsulfonyl, (y) a C.sub.6-10 aryl, (z) a C.sub.6-10 aryloxy, (aa) a 5- to 7-membered heterocyclic group having 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur in addition to carbon atoms, said heterocyclic group being optionally fused with a benzene ring, (bb) thiocarbamoyl, (cc) mono-C.sub.1-6 alkylthio-carbamoyl, (dd) di-C.sub.1-6 alkylthio-carbamoyl, (ee) C.sub.6-10 aryl-carbamoyl and (ff) C.sub.6-10 aryl-thiocarbamoyl, (2) a C.sub.1-6 alkylenedioxy group which may have 1 to 5 substituents selected from the group consisting of (a) a halogen, (b) a C.sub.1-3 alkylenedioxy, (c) a nitro, (d) a cyano, (e) a C.sub.1-6 alkyl optionally having 1 to 3 halogen atoms, (f) a C.sub.3-6 cycloalkyl, (g) a C.sub.1-6 alkoxy which may be substituted with amino, mono- or di-C.sub.1-6 alkylamino or C.sub.1-6 alkoxycarbonyl, and optionally having 1 to 3 halogen atoms, (h) a C.sub.1-6 alkylthio optionally having 1 to 3 halogen atoms, (i) a hydroxyl, (j) an amino, (k) a mono-C.sub.1-6 alkylamino, (l) a di-C.sub.1-6 alkylamino, (m) a C.sub.1-6 alkyl-carbonyl, (n) a C.sub.1-6 alkyl-carbonyloxy, (o) a C.sub.1-6 alkyl-carbonyloxy-C.sub.1-3 alkyl, (p) a carboxyl, (q) a C.sub.1-6 alkoxy-carbonyl, (r) a mono-C.sub.1-6 alkylamino-carbonyl, (s) a di-C.sub.1-6 alkylamino-carbonyl, (t) a carbamoyl, (u) a mono-C.sub.1-6 alkyl-carbamoyl, (v) a di-C.sub.1-6 alkyl-carbamoyl, (w) a sulfo, (x) a C.sub.1-6 alkylsulfonyl, (y) a C.sub.6-10 aryl, (z) a C.sub.6-10 aryloxy, (aa) a 5- to 7-membered heterocyclic group having 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur in addition to carbon atoms, said heterocyclic group being optionally fused with a benzene ring, (bb) thiocarbamoyl, (cc) mono-C.sub.1-6 alkylthio-carbamoyl, (dd) di-C.sub.1-6 alkylthio-carbamoyl, (ee) C.sub.6-10 aryl-carbamoyl and (ff) C.sub.6-10 aryl-thiocarbamoyl, or (3) a C.sub.1-6 alkyleneoxy group which may have 1 to 5 substituents selected from the group consisting of (a) a halogen, (b) a C.sub.1-3 alkylenedioxy, (c) a nitro, (d) a cyano, (e) a C.sub.1-6 alkyl optionally having 1 to 3 halogen atoms, (f) a C.sub.3-6 cycloalkyl, (g) a C.sub.1-6 alkoxy which may be substituted with amino, mono- or di-C.sub.1-6 alkylamino or C.sub.1-6 alkoxycarbonyl, and optionally having 1 to 3 halogen atoms, (h) a C.sub.1-6 alkylthio optionally having 1 to 3 halogen atoms, (i) a hydroxyl, (j) an amino, (k) a mono-C.sub.1-6 alkylamino, (l) a di-C.sub.1-6 alkylamino, (m) a C.sub.1-6 alkyl-carbonyl, (n) a C.sub.1-6 alkyl-carbonyloxy, (o) a C.sub.1-6 alkyl-carbonyloxy-C.sub.1-3 alkyl, (p) a carboxyl, (q) a C.sub.1-6 alkoxy-carbonyl, (r) a mono-C.sub.1-6 alkylamino-carbonyl, (s) a di-C.sub.1-6 alkylamino-carbonyl, (t) a carbamoyl, (u) a mono-C.sub.1-6 alkyl-carbamoyl, (v) a di-C.sub.1-6 alkyl-carbamoyl, (w) a sulfo, (x) a C.sub.1-6 alkylsulfonyl, (y) a C.sub.6-10 aryl, (z) a C.sub.6-10 aryloxy, (aa) a 5- to 7-membered heterocyclic group having 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur in addition to carbon atoms, said heterocyclic group being optionally fused with a benzene ring, (bb) thiocarbamoyl, (cc) mono-C.sub.1-6 alkylthio-carbamoyl, (dd) di-C.sub.1-6 alkylthio-carbamoyl, (ee) C.sub.6-10 aryl-carbamoyl and (ff) C.sub.6-10 aryl-thiocarbamoyl; and PA1 ring A is a benzene ring which may have 1 or 2 substituents selected from the group consisting of (1) a hydrogen, (2) a halogen, (3) a C.sub.1-16 acyclic or cyclic hydrocarbon group which may have 1 to 5 substituents selected from the group consisting of (i) a halogen, (ii) a C.sub.1-3 alkylenedioxy, (iii) a nitro, (iv) a cyano, (v) a C.sub.1-6 alkyl optionally having 1 to 3 halogen atoms, (vi) a C.sub.3-6 cycloalkyl, (vii) a C.sub.1-6 alkoxy which may be substituted with amino, mono- or di-C.sub.1-6 alkylamino or C.sub.1-6 alkoxycarbonyl, and optionally having 1 to 3 halogen atoms, (viii) a C.sub.1-6 alkylthio optionally having 1 to 3 halogen atoms, (ix) a hydroxyl, (x) an amino, (xi) a mono-C.sub.1 l.sub.6 alkylamino, (xii) a di-C.sub.1-6 alkylamino, (xiii) a C.sub.1-6 alkyl-carbonyl, (xiv) a C.sub.1-6 alkyl-carbonyloxy, (xv) a C.sub.1-6 alkyl-carbonyloxy-C.sub.1-3 alkyl, (xvi) a carboxyl, (xvii) a C.sub.1-6 alkoxy-carbonyl, (xviii) a mono-C.sub.1-6 alkylamino-carbonyl, (xix) a di-C.sub.1-6 alkylamino-carbonyl, (xx) a carbamoyl, (xxi) a mono-C.sub.1-6 alkyl-carbamoyl, (xxii) a di-C.sub.1-6 alkyl-carbamoyl, (xxiii) a sulfo, (xxiv) a C.sub.1-6 alkylsulfonyl, (xxv) a C.sub.6-10 aryl, (xxvi) a C.sub.6-10 aryloxy; (xxvii) a 5- to 7-membered heterocyclic group having 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur in addition to carbon atoms, said heterocyclic group being optionally fused with a benzene ring, (xxviii) thiocarbamoyl, (xxix) mono-C.sub.1-6 alkylthio-carbamoyl, (xxx) di-C.sub.1-6 alkylthio-carbamoyl, (xxxi) C.sub.6-10 aryl-carbamoyl and (xxxii) C.sub.6-10 aryl-thiocarbamoyl, PA1 3. A compound of the formula: ##STR14## wherein Q is (1) CR.sup.4 wherein R.sup.4 is (i) a hydrogen atom, (ii) a halogen atom, (iii) an optionally substituted hydrocarbon group or (iv) an optionally substituted hydroxyl group, or (2) N(O)p wherein p is 0 or 1; PA1 X is C.dbd.O or C.dbd.S; PA1 Y is (1) CH.sub.2, (2) S(O)q wherein q is an integer of 0 to 2, or (3) NR.sup.5 wherein R.sup.5 is (i) a hydrogen atom, (ii) an optionally substituted hydrocarbon group or (iii) an acyl group; PA1 m and n each represents 0 or 1, PA1 Ar is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group; PA1 one of R.sup.1 and R.sup.2 is a hydrogen atom, a halogen atom, a hydroxyl group, an optionally substituted lower alkyl group, or an optionally substituted lower alkoxy group; PA1 the other is a halogen atom, a hydroxyl group, an optionally substituted lower alkyl group, or an optionally substituted lower alkoxy group; or PA1 R.sup.1 and R.sup.2 taken together with adjacent --c.dbd.c-- form a ring; and PA1 ring A is a benzene ring which may be substituted in addition to R.sup.1 and R.sup.2 ; PA1 4. A compound as described in the above item 3 wherein PA1 Q is (A) CR.sup.4 wherein R.sup.4 is (1) a hydrogen atom, (2) a halogen atom, (3) a C.sub.1-16 acyclic or cyclic hydrocarbon group which may have 1 to 5 substituents selected from the group consisting of (i) a halogen, (ii) a C.sub.1-3 alkylenedioxy, (iii) a nitro, (iv) a cyano, (v) a C.sub.1-6 alkyl optionally having 1 to 3 halogen atoms, (vi) a C.sub.3-6 cycloalkyl, (vii) a C.sub.1-6 alkoxy which may be substituted with amino, mono- or di-C.sub.1-6 alkylamino or C.sub.1-6 alkoxycarbonyl, and optionally having 1 to 3 halogen atoms, (viii) a C.sub.1-6 alkylthio optionally having 1 to 3 halogen atoms, (ix) a hydroxyl, (x) an amino, (xi) a mono-C.sub.1-6 alkylamino, (xii) a di-C.sub.1-6 alkylamino, (xiii) a C.sub.1-6 alkyl-carbonyl, (xiv) a C.sub.1-6 alkyl-carbonyloxy, (xv) a C.sub.1-6 alkyl-carbonyloxy-C.sub.1-3 alkyl, (xvi) a carboxyl, (xvii) a C.sub.1-6 alkoxy-carbonyl, (xviii) a mono-C.sub.1-6 alkylamino-carbonyl, (xix) a di-C.sub.1-6 alkylamino-carbonyl, (xx) a carbamoyl, (xxi) a mono-C.sub.1-6 alkyl-carbamoyl, (xxii) a di-C.sub.1-6 alkyl-carbamoyl, (xxiii) a sulfo, (xxiv) a C.sub.1-6 alkylsulfonyl, (xxv) a C.sub.6-10 aryl, (xxvi) a C.sub.6-10 aryloxy, (xxvii) a 5- to 7-membered heterocyclic group having 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur in addition to carbon atoms, said heterocyclic group being optionally fused with a benzene ring, (xxviii) thiocarbamoyl, (xxix) mono-C.sub.1-6 alkylthio-carbamoyl, (xxx) di-C.sub.1-6 alkylthio-carbamoyl, (xxxi) C.sub.6-10 aryl-carbamoyl and (xxxii) C.sub.6-10 aryl-thiocarbamoyl, or (4) a hydroxyl group which may be substituted with a C.sub.1-16 acyclic or cyclic hydrocarbon group which may have 1 to 5 substituents selected from the group consisting of (i) a halogen, (ii) a C.sub.1-3 alkylenedioxy, (iii) a nitro, (iv) a cyano, (v) a C.sub.1-6 alkyl optionally having 1 to 3 halogen atoms, (vi) a C.sub.3-6 cycloalkyl, (vii) a C.sub.1-6 alkoxy which may be substituted with amino, mono- or di-C.sub.1-6 alkylamino or C.sub.1-6 alkoxycarbonyl, and optionally having 1 to 3 halogen atoms, (viii) a C.sub.1-6 alkylthio optionally having 1 to 3 halogen atoms, (ix) a hydroxyl, (x) an amino, (xi) a mono-C.sub.1-6 alkylamino, (xii) a di-C.sub.1-6 alkylamino, (xiii) a C.sub.1-6 alkyl-carbonyl, (xiv) a C.sub.1-6 alkyl-carbonyloxy, (xv) a C.sub.1-6 alkyl-carbonyloxy-C.sub.1-3 alkyl, (xvi) a carboxyl, (xvii) a C.sub.1-6 alkoxy-carbonyl, (xviii) a mono-C.sub.1-6 alkylamino-carbonyl, (xix) a di-C.sub.1-6 alkylamino-carbonyl, (xx) a carbamoyl, (xxi) a mono-C.sub.1-6 alkyl-carbamoyl, (xxii) a di-C.sub.1-6 alkyl-carbamoyl, (xxiii) a sulfo, (xxiv) a C.sub.1-6 alkylsulfonyl, (xxv) a C.sub.6-10 aryl, (xxvi) a C.sub.6-10 aryloxy, (xxvii) a 5- to 7-membered heterocyclic group having 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur in addition to carbon atoms, said heterocyclic group being optionally fused with a benzene ring, (xxviii) thiocarbamoyl, (xxix) mono-C.sub.1-6 alkylthio-carbamoyl, (xxx) di-C.sub.1-6 alkylthio-carbamoyl, (xxxi) C.sub.6-10 aryl-carbamoyl and (xxxii) C.sub.6-10 aryl-thiocarbamoyl; PA1 or (B) N(O)p wherein p is 0 or 1; PA1 Y is (1) CH.sub.2, (2) S(O)q wherein q is an integer of 0 to 2, or (3) NR.sup.5 wherein R.sup.5 is (i) a hydrogen, (ii) a C.sub.1-16 acyclic or cyclic hydrocarbon group which may have 1 to 5 substituents selected from the group consisting of (a) a halogen, (b) a C.sub.1-3 alkylenedioxy, (c) a nitro, (d) a cyano, (e) a C.sub.1-6 alkyl optionally having 1 to 3 halogen atoms, (f) a C.sub.3-6 cycloalkyl, (g) a C.sub.1-6 alkoxy which may be substituted with amino, mono- or di-C.sub.1-6 alkylamino or C.sub.1-6 alkoxycarbonyl, and optionally having 1 to 3 halogen atoms, (h) a C.sub.1-6 alkylthio optionally having 1 to 3 halogen atoms, (i) a hydroxyl, (j) an amino, (k) a mono-C.sub.1-6 alkylamino, (l) a di-C.sub.1-6 alkylamino, (m) a C.sub.1-6 alkyl-carbonyl, (n) a C.sub.1-6 alkyl-carbonyloxy, (o) a C.sub.1-6 alkyl-carbonyloxy-C.sub.1-3 alkyl, (p) a carboxyl, (q) a C.sub.1-6 alkoxy-carbonyl, (r) a mono-C.sub.1-6 alkylamino-carbonyl, (s) a di-C.sub.1-6 alkylamino-carbonyl, (t) a carbamoyl, (u) a mono-C.sub.1-6 alkyl-carbamoyl, (v) a di-C.sub.1-6 alkyl-carbamoyl, (w) a sulfo, (x) a C.sub.1-6 alkylsulfonyl, (y) a C.sub.6-10 aryl, (z) a C.sub.6-10 aryloxy, (aa) a 5- to 7-membered heterocyclic group having 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur in addition to carbon atoms, said heterocyclic group being optionally fused with a benzene ring, (bb) thiocarbamoyl, (cc) mono-C.sub.1-6 alkylthio-carbamoyl, (dd) di-C.sub.1-6 alkylthio-carbamoyl, (ee) C.sub.6-10 aryl-carbamoyl and (ff) C.sub.6-10 aryl-thiocarbamoyl, (iii) --(C.dbd.O)--R.sup.7 wherein R.sup.7 is a hydrogen or a C.sub.1-16 acyclic or cyclic hydrocarbon group which may have 1 to 5 substituents selected from the group consisting of (a) a halogen, (b) a C.sub.1-3 alkylenedioxy, (c) a nitro, (d) a cyano, (e) a C.sub.1-6 alkyl optionally having 1 to 3 halogen atoms, (f) a C.sub.3-6 cycloalkyl, (g) a C.sub.1-6 alkoxy optionally having 1 to 3 halogen atoms, (h) a C.sub.1-6 alkylthio optionally having 1 to 3 halogen atoms, (i) a hydroxyl, (j) an amino, (k) a mono-C.sub.1-6 alkylamino, (l) a di-C.sub.1-6 alkylamino, (m) 5- or 6-membered cyclicamino optionally having carboxyl or oxo, (n) --NHCOOR.sup.6 wherein R.sup.6 is a C.sub.1-16 acyclic or cyclic hydrocarbon group which may have 1 to 5 substituents selected from the group consisting of (n-1) a halogen, (n-2) a C.sub.1-3 alkylenedioxy, (n-3) a nitro, (n-4) a cyano, (n-5) a C.sub.1-6 alkyl optionally having 1 to 3 halogen atoms, (n-6) a C.sub.3-6 cycloalkyl, (n-7) a C.sub.1-6 alkoxy which may be substituted with amino, mono- or di-C.sub.1-6 alkylamino or C.sub.1-6 alkoxycarbonyl, and optionally having 1 to 3 halogen atoms, (n-8) a C.sub.1-6 alkylthio optionally having 1 to 3 halogen atoms, (n-9) a hydroxyl, (n-10) an amino, (n-11) a mono-C.sub.1-6 alkylamino, (n-12) a di-C.sub.1-6 alkylamino, (n-13) a C.sub.1-6 alkyl-carbonyl, (n-14) a C.sub.1-6 alkyl-carbonyloxy, (n-15) a C.sub.1-6 alkyl-carbonyloxy-C.sub.1-3 alkyl, (n-16) a carboxyl, (n-17) a C.sub.1-6 alkoxy-carbonyl, (n-18) a mono-C.sub.1-6 alkylamino-carbonyl, (n-19) a di-C.sub.1-6 alkylamino-carbonyl, (n-20) a carbamoyl, (n-21) a mono-C.sub.1-6 alkyl-carbamoyl, (n-22) a di-C.sub.1-6 alkyl-carbamoyl, (n-23) a sulfo, (n-24) a C.sub.1-6 alkylsulfonyl, (n-25) a C.sub.6-10 aryl, (n-26) a C.sub.6-10 aryloxy, (n-27) a 5- to 7-membered heterocyclic group having 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur in addition to carbon atoms, said heterocyclic group being optionally fused with a benzene ring, (n-28) thiocarbamoyl, (n-29) mono-C.sub.1-6 alkylthio-carbamoyl, (n-30) di-C.sub.1-6 alkylthio-carbamoyl, (n-31) C.sub.6-10 aryl-carbamoyl and (n-32) C.sub.6-10 aryl-thiocarbamoyl, (o) --NHCONHR.sup.6 wherein R.sup.6 is as defined above, (p) --NHCOR.sup.6 wherein R.sup.6 is as defined above, (q) --NHSO.sub.2 R.sup.6 wherein R.sup.6 is as defined above, (r) a C.sub.1-6 alkyl-carbonyl, (s) a C.sub.1-6 alkyl-carbonyloxy, (t) a C.sub.1-6 alkyl-carbonyloxy-C.sub.1-3 alkyl, (u) a carboxyl, (v) a C.sub.1-6 alkoxy-carbonyl, (w) a mono-C.sub.1-6 alkylamino-carbonyl, (x) a di-C.sub.1-6 alkylamino-carbonyl, (y) a carbamoyl, (z) a mono-C.sub.1-6 alkyl-carbamoyl, (aa) a di-C.sub.1-6 alkyl-carbamoyl, C.sub.6-10 aryl-carbamoyl, (bb) a sulfo, (cc) a C.sub.1-6 alkylsulfonyl, (dd) a C.sub.6-10 aryl, (ee) a C.sub.6-10 aryloxy, (ff) a 5- to 7-membered heterocyclic group having 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur in addition to carbon atoms, said heterocyclic group being optionally fused with a benzene ring, (gg) C.sub.7-11 aralkyloxy-carbonyl, (hh) thiocarbamoyl, (ii) mono-C.sub.1-6 alkylthio-carbamoyl, (jj) di-C.sub.1-6 alkylthio-carbamoyl, (kk) C.sub.6-10 aryl-carbamoyl and (11) C.sub.6-10 aryl-thiocarbamoyl, (iv) --SO.sub.2 --R.sup.7 wherein R.sup.7 is as defined above, (v) --SO--R.sup.7 wherein R.sup.7 is as defined above, (vi) --(C.dbd.O)NR.sup.8 --R.sup.7 wherein R.sup.7 is as defined above, R.sup.8 is hydrogen or C.sub.1-6 alkyl or (vii) --(C.dbd.O)O--R.sup.7 wherein R.sup.7 is as defined above, PA1 5. A compound as described in the above item 3 wherein PA1 Q is CR.sup.4 wherein R.sup.4 is as defined in the above item 3, PA1 6. A compound as described in the above item 3 wherein PA1 X is C.dbd.O, PA1 7. A compound as described in the above item 3 wherein PA1 Y is NR.sup.5 wherein R.sup.5 is as described in the above item 3, PA1 8. A compound as described in the above item 3 wherein PA1 Y is CH.sub.2, PA1 9. A compound as described in the above item 3 wherein PA1 Ar is 3- to 14-membered aromatic group which may have 1 to 5 substituents selected from the group consisting of (i) a halogen, (ii) a C.sub.1-3 alkylenedioxy, (iii) a nitro, (iv) a cyano, (v) a C.sub.1-6 alkyl optionally having 1 to 3 halogen atoms, (vi) a C.sub.2-6 alkenyl optionally having 1 to 3 halogen atoms, (vii) a C.sub.2-6 alkynyl optionally having 1 to 3 halogen atoms, (viii) a C.sub.3-6 cycloalkyl, (ix) a C.sub.1-6 alkoxy which may be substituted with amino, mono- or di-C.sub.1-6 alkylamino or C.sub.1-6 alkoxycarbonyl, and optionally having 1 to 3 halogen atoms, (x) a C.sub.1-6 alkylthio optionally having 1 to 3 halogen atoms, (xi) a hydroxyl, (xii) an amino, (xiii) a mono-C.sub.1-6 alkylamino, (xiv) a di-C.sub.1-6 alkylamino, (xv) 5- or 6-membered cyclic amino, (xvi) --NHCOOR.sup.6 wherein R.sup.6 is a C.sub.1-16 acyclic or cyclic hydrocarbon group which may have 1 to 5 substituents selected from the group consisting of (a) a halogen, (b) a C.sub.1-3 alkylenedioxy, (c) a nitro, (d) a cyano, (e) a C.sub.1-6 alkyl optionally having 1 to 3 halogen atoms, (f) a C.sub.3-6 cycloalkyl, (g) a C.sub.1-6 alkoxy optionally having 1 to 3 halogen atoms, (h) a C.sub.1-6 alkylthio optionally having 1 to 3 halogen atoms, (i) a hydroxyl, (j) an amino, (k) a mono-C.sub.1-6 alkylamino, (l) a di-C.sub.1-6 alkylamino, (m) a C.sub.1-6 alkyl-carbonyl, (n) a C.sub.1-6 alkyl-carbonyloxy, (o) a C.sub.1-6 alkyl-carbonyloxy-C.sub.1-3 alkyl, (p) a carboxyl, (q) a C.sub.1-6 alkoxy-carbonyl, (r) a mono-C.sub.1-6 alkylamino-carbonyl, (s) a di-C.sub.1-6 alkylamino-carbonyl, (t) a carbamoyl, (u) a mono-C.sub.1-6 alkyl-carbamoyl, (v) a di-C.sub.1-6 alkyl-carbamoyl, (w) a sulfo, (x) a C.sub.1-6 alkylsulfonyl, (y) a C.sub.6-10 aryl, (z) a C.sub.6-10 aryloxy, (aa) a 5- to 7-membered heterocyclic group having 1 to 4 hetero atoms selected from the group consisting of a nitrogen, an oxygen and a sulfur in addition to carbon atoms, said heterocyclic group being optionally fused with a benzene ring, (bb) thiocarbamoyl, (cc) mono-C.sub.1-6 alkylthio-carbamoyl, (dd) di-C.sub.1-6 alkylthio-carbamoyl, (ee) C.sub.6-10 aryl-carbamoyl and (ff) C.sub.6-10 aryl-thiocarbamoyl, (xvii) --NHCONHR.sup.6 wherein R.sup.6 is as defined above, (xviii) --NHCOR.sup.6 wherein R is as defined above, (xix) --NHSO.sub.2 R.sup.6 wherein R.sup.6 is as defined above, (xx) a C.sub.1-6 alkyl-carbonyl, (xxi) a carboxyl, (xxii) a C.sub.1-6 alkoxy-carbonyl, (xxiii) a carbamoyl, (xxiv) a mono-C.sub.1-6 alkyl-carbamoyl, (xxv) a di-C.sub.1-6 alkyl-carbamoyl, (xxvi) a C.sub.6-10 aryl-carbamoyl, (xxvii) a sulfo, (xxviii) a C.sub.1-6 alkylsulfonyl, (xxix) a C.sub.6-10 aryl, (xxx) a C.sub.6-10 aryloxy, (xxxi) C.sub.7-16 aralkyloxy, (xxxii) thiocarbamoyl, (xxxiii) mono-C.sub.1-6 alkylthio-carbamoyl, (xxxiv) di-C.sub.1-6 alkylthio-carbamoyl, (xxxv) C.sub.6-10 aryl-carbamoyl and (xxxvi) C.sub.6-10 aryl-thiocarbamoyl, PA1 10. A compound as described in the above item 4 wherein PA1 Ar is a phenyl group which may have 1 to 5 substituents selected from the group consisting of (i) a halogen, (ii) a C.sub.1-3 alkylenedioxy, (iii) a nitro, (iv) a cyano, (v) a C.sub.1-6 alkyl optionally having 1 to 3 halogen atoms, (vi) a C.sub.2-6 alkenyl optionally having 1 to 3 halogen atoms, (vii) a C.sub.2-6 alkynyl optionally having 1 to 3 halogen atoms, (viii) a C.sub.3-6 cycloalkyl, (ix) a C.sub.1-6 alkoxy which may be substituted with amino, mono- or di-C.sub.1-6 alkylamino or C.sub.1-6 alkoxycarbonyl, and optionally having 1 to 3 halogen atoms, (x) a C.sub.1-6 alkylthio optionally having 1 to 3 halogen atoms, (xi) a hydroxyl, (xii) an amino, (xiii) a mono-C.sub.1-6 alkylamino, (xiv) a di-C.sub.1-6 alkylamino, (xv) 5- or 6-membered cyclic amino, (xvi) --NHCOOR.sup.6 wherein R.sup.6 is a C.sub.1-16 acyclic or cyclic hydrocarbon group which may have 1 to 5 substituents selected from the group consisting of (a) a halogen, (b) a C.sub.1-3 alkylenedioxy, (c) a nitro, (d) a cyano, (e) a C.sub.1-6 alkyl optionally having 1 to 3 halogen atoms, (f) a C.sub.3-6 cycloalkyl, (g) a C.sub.1-6 alkoxy optionally having 1 to 3 halogen atoms, (h) a C.sub.1-6 alkylthio optionally having 1 to 3 halogen atoms, (i) a hydroxyl, (j) an amino, (k) a mono-C.sub.1-6 alkylamino, (l) a di-C.sub.1-6 alkylamino, (m) a C.sub.1-6 alkyl-carbonyl, (n) a C.sub.1-6 alkyl-carbonyloxy, (o) a C.sub.1-6 alkyl-carbonyloxy-C.sub.1-3 alkyl, (p) a carboxyl, (q) a C.sub.1-6 alkoxy-carbonyl, (r) a mono-C.sub.1-6 alkylamino-carbonyl, (s) a di-C.sub.1-6 alkylamino-carbonyl, (t) a carbamoyl, (u) a mono-C.sub.1-6 alkyl-carbamoyl, (v) a di-C.sub.1-6 alkyl-carbamoyl, (w) a sulfo, (x) a C.sub.1-6 alkylsulfonyl, (y) a C.sub.6-10 aryl, (z) a C.sub.6-10 aryloxy, (aa) a 5- to 7-membered heterocyclic group having 1 to 4 hetero atoms selected from the group consisting of a nitrogen, an oxygen and a sulfur in addition to carbon atoms, said heterocyclic group being optionally fused with a benzene ring, (bb) thiocarbamoyl, (cc) mono-C.sub.1-6 alkylthio-carbamoyl, (dd) di-C.sub.1-6 alkylthio-carbamoyl, (ee) C.sub.6-10 aryl-carbamoyl and (ff) C.sub.6-10 aryl-thiocarbamoyl, (xvii) --NHCONHR.sup.6 wherein R.sup.6 is as defined above, (xviii) --NHCOR.sup.6 wherein R.sup.6 is as defined above, (xix) --NHSO.sub.2 R.sup.6 wherein R.sup.6 is as defined above, (xx) a C.sub.1-6 alkyl-carbonyl, (xxi) a carboxyl, (xxii) a C.sub.1-6 alkoxy-carbonyl, (xxiii) a carbamoyl, (xxiv) a mono-C.sub.1-6 alkyl-carbamoyl, (xxv) a di-C.sub.1-6 alkyl-carbamoyl, (xxvi) a C.sub.6-10 aryl-carbamoyl, (xxvii) a sulfo, (xxviii) a C.sub.1-6 alkylsulfonyl, (xxix) a C.sub.6-10 aryl, (xxx) a C.sub.6-10 aryloxy, (xxxi) C.sub.7-16 aralkyloxy, (xxxii) thiocarbamoyl, (xxxiii) mono-C.sub.1-6 alkylthio-carbamoyl, (xxxiv) di-C.sub.1-6 alkylthio-carbamoyl, (xxxv) C.sub.6-10 aryl-carbamoyl and (xxxvi) C.sub.6-10 aryl-thiocarbamoyl, PA1 11. A compound as described in the above item 4, PA1 wherein ##STR15## wherein R.sup.3 is (1) a hydrogen atom, (2) a halogen atom, (3) a C.sub.1-16 acyclic or cyclic hydrocarbon group which may have 1 to 5 substituents selected from the group consisting of (a) a halogen, (b) a C.sub.1-3 alkylenedioxy, (c) a nitro, (d) a cyano, (e) a C.sub.1-6 alkyl optionally having 1 to 3 halogen atoms, (f) a C.sub.3-6 cycloalkyl, (g) a C.sub.1-6 alkoxy which may be substituted with amino, mono- or di-C.sub.1-6 alkylamino or C.sub.1-6 alkoxycarbonyl, and optionally having 1 to 3 halogen atoms, (h) a C.sub.1-6 alkylthio optionally having 1 to 3 halogen atoms, (i) a hydroxyl, (j) an amino, (k) a mono-C.sub.1-6 alkylamino, (l) a di-C.sub.1-6 alkylamino, (m) a C.sub.1-6 alkyl-carbonyl, (n) a C.sub.1-6 alkyl-carbonyloxy, (o) a C.sub.1-6 alkyl-carbonyloxy-C.sub.1-3 alkyl, (p) a carboxyl, (q) a C.sub.1-6 alkoxy-carbonyl, (r) a mono-C.sub.1-6 alkylamino-carbonyl, (s) a di-C.sub.1-6 alkylamino-carbonyl, (t) a carbamoyl, (u) a mono-C.sub.1-6 alkyl-carbamoyl, (v) a di-C.sub.1-6 alkyl-carbamoyl, (w) a sulfo, (x) a C.sub.1-6 alkylsulfonyl, (y) a C.sub.6-10 aryl, (z) a C.sub.6-10 aryloxy, (aa) a 5- to 7-membered heterocyclic group having 1 to 3 hetero atoms selected from nitrogen, oxygen and sulfur in addition to carbon atoms, said heterocyclic group being optionally fused with a benzene ring,an optionally substituted hydrocarbon group, (bb) thiocarbamoyl, (cc) mono-C.sub.1-6 alkylthio-carbamoyl, (dd) di-C.sub.1-6 alkylthio-carbamoyl, (ee) C.sub.6-10 aryl-carbamoyl and (ff) C.sub.6-10 aryl-thiocarbamoyl or (4) a hydroxyl group which may be substituted with a C.sub.1-6 acyclic or cyclic hydrocarbon group which may have 1 to 5 substituents selected from the group consisting of (i) a halogen, (ii) a C.sub.1-3 alkylenedioxy, (iii) a nitro, (iv) a cyano, (v) a C.sub.1-6 alkyl optionally having 1 to 3 halogen atoms, (vi) a C.sub.3-6 cycloalkyl, (vii) a C.sub.1-6 alkoxy which may be substituted with amino, mono- or di-C.sub.1-6 alkylamino or C.sub.1-6 alkoxycarbonyl, and optionally having 1 to 3 halogen atoms, (viii) a C.sub.1-6 alkylthio optionally having 1 to 3 halogen atoms, (ix) a hydroxyl, (x) an amino, (xi) a mono-C.sub.1-6 alkylamino, (xii) a di-C.sub.1-6 alkylamino, (xiii) a C.sub.1-6 alkyl-carbonyl, (xiv) a C.sub.1-6 alkyl-carbonyloxy, (xv) a C.sub.1-6 alkyl-carbonyloxy-C.sub.1-3 alkyl, (xvi) a carboxyl, (xvii) a C.sub.1-6 alkoxy-carbonyl, (xviii) a mono-C.sub.1-6 alkylamino-carbonyl, (xix) a di-C.sub.1-6 alkylamino-carbonyl, (xx) a carbamoyl, (xxi) a mono-C.sub.1-6 alkyl-carbamoyl, (xxii) a di-C.sub.1-6 alkyl-carbamoyl, (xxiii) a sulfo, (xxiv) a C.sub.1-6 alkylsulfonyl, (xxv) a C.sub.6-10 aryl, (xxvi) a C.sub.6-10 aryloxy, (xxvii) a 5- to 7-membered heterocyclic group having 1 to 3 hetero atoms selected from nitrogen, oxygen and sulfur in addition to carbon atoms, said heterocyclic group being optionally fused with a benzene ring, (xxviii) thiocarbamoyl, (xxix) mono-C.sub.1-6 alkylthio-carbamoyl, (xxv) di-C.sub.1-6 alkylthio-carbamoyl, (xxvi) C.sub.6-10 aryl-carbamoyl and (xxvii) C.sub.6-10 aryl-thiocarbamoyl, PA1 12. A compound as described in the above item 11 wherein PA1 R.sup.3 is a hydrogen, PA1 13. A compound as described in the above item 3 wherein PA1 Q is (1) CR 4 wherein R.sup.4' is (i) a C.sub.1-6 alkyl group which may be substituted with a di-C.sub.1-6 alkylamino group, (ii) a halogen atom, or (iii) a C.sub.1-6 alkoxy group, or (2) N; PA1 X is C.dbd.O; PA1 Y is NR.sup.5' wherein R.sup.5' is (i) a hydrogen, (ii) a C.sub.1-6 alkyl group which may be substituted with (a) a morpholino, (b) a carboxyl, (c) a C.sub.1-6 alkoxy-carbonyl, or (d) a phenyl which may be substituted with C.sub.1-6 alkoxy, or (iii) COR.sup.7" wherein R.sup.7" is (a) a hydrogen, (b) C.sub.1-6 alkyl which may be substituted with a carboxyl or a benzyloxycarbonyl, or a di-C.sub.1-6 alkylamino; PA1 m and n each represents 0; PA1 Z.sup.2 is (1) C.dbd.O, (2) CH.sub.2, (3) (CH.sub.2).sub.2, (4) (CH.sub.2).sub.3, or (5) CH--OH; PA1 Ar is (1) a phenyl group which may be substituted with (a) a halogen, (b) a C.sub.1-6 alkylenedioxy, (c) a C.sub.1-6 alkoxy which may be substituted with (c-1) a halogen, (c-2) a di-C.sub.1-6 alkylamino or (c-3) a C.sub.1-6 alkoxy-carbonyl, (d) a C.sub.7-11 aralkyloxy, (e) C.sub.1-6 alkyl which may be substituted with a halogen or (f) hydroxyl, (2) an optionally oxidized pyridyl group, or (3) a pyridinium group which may be substituted with C.sub.1-6 alkyl; PA1 one of R.sup.1 and R.sup.2 is (1) a hydrogen, (2) a C.sub.1-6 alkyl, (3) a C.sub.1-6 alkoxy which may be substituted with (a) a C.sub.1-6 alkoxy-carbonyl, (b) a C.sub.7-11 aralkyl or (c) a carboxyl, or (4) a hydroxyl; PA1 the other is (1) a C.sub.1-6 alkyl, (2) a C.sub.1-6 alkoxy which may be substituted with (a) a C.sub.1-6 alkoxy-carbonyl or (b) a carboxyl, or (3) a hydroxyl; or PA1 R.sup.1 and R.sup.2 taken together with adjacent --c.dbd.c-- form a C.sub.1-6 alkylenedioxy group, or a C.sub.1-6 alkyleneoxy group; or ring A is a benzene ring which may have a C.sub.1-6 alkoxy group, in addition to R.sup.1 and R.sup.2, and a C.sub.1-6 alkoxy group on ring A and a C.sub.1-6 alkoxy group of R.sup.1 may be taken together form a C.sub.1-6 alkylenedioxy group; PA1 14. A compound as described in the above item 13 wherein PA1 Q is CH or N; PA1 X is C.dbd.O; PA1 m and n each represents 0; PA1 Z.sup.2 is CH.sub.2 ; and PA1 R.sup.1 and R.sup.2 taken together with adjacent --c.dbd.c-- form a C.sub.1-6 alkylenedioxy group, PA1 15. A process for producing a compound of the formula: ##STR16## wherein all symbols have the same meanings as defined in the above item 3, or a salt thereof, which comprises subjecting a compound of the formula: ##STR17## wherein all symbols have the same meaning as defined in the above item 3, or a salt thereof, to lactamization reaction, optionally followed by introducing a substituent R.sup.5 into the resulting lactam, PA1 16. A compound of the formula: ##STR18## wherein all symbols have the same meaning as defined in the above item 3, or a salt thereof; provided that (1) when both of R.sup.1 and R.sup.2 are methoxy groups, Q is CR.sup.4, X is C.dbd.O, Z.sup.2 is a methylene, and m is 0, Ar is not any of phenyl, 3,4,5-trimethoxyphenyl, 4,5-dimethoxy-2-methylphenyl and 1,3-benzodioxol-5-yl; that (2) when R.sup.1 is a hydroxyl or a methoxy, Q is CR.sup.4, X is C.dbd.O, Z.sup.2 is a methylene, and m is 0, Ar is not 1,3-benzodioxol-5-yl; and that (3) when R.sup.1 and R.sup.2 taken together represent a methylenedioxy which may be substituted with an oxygen atom, Q is CR.sup.4, X is C.dbd.O, Z.sup.2 is a methylene, and m is 0, Ar is not any of 1,3-benzodioxol-5-yl, 6-bromo-1,3-benzodioxol-5-yl, 7-hydroxyl-1,3-benzodioxol-5-yl, 7-acetoxy-1,3-benzodioxol-5-yl, and 7-methoxy-1,3-benzodioxol-5-yl, PA1 17. A pharmaceutical composition comprising a compound of the above item 1, PA1 18. A cell differentiation inducing factor composition comprising the compound of the above item 1, PA1 19. A composition of the above item 17 which enhances cell differentiation inducing factor, PA1 20. A composition for treating or preventing neuropathy or bone and joint disease which comprises the compound of the above item 1, PA1 21. A bone formation promoting composition comprising the compound of the above item 1, PA1 22. A cartilage disruption inhibitory composition comprising the compound of the above item 1, PA1 23. A method of treating or preventing neuropathy or bone-and-joint disease which comprises administering to a mammal in need thereof an effective amount of a compound of the formula: ##STR19## wherein Q is an optionally substituted carbon atom or N(O)p wherein p is 0 or 1; PA1 Y is an optionally substituted methylene group, S(O)q wherein q is an integer of 0 to 2, or an optionally substituted imino group; PA1 Z.sup.1 is a C.sub.1-3 alkylene group which may have an oxo group or a thioxo group and may contain etherified oxygen or sulfur within the carbon chain; PA1 Z.sup.2 is an optionally substituted C.sub.1-3 alkylene group; PA1 Ar is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group; PA1 one of R.sup.1 and R.sup.2 is a hydrogen atom, a halogen atom, a hydroxyl group, an optionally substituted lower alkyl group or an optionally substituted lower alkoxy group; PA1 the other is a halogen atom, a hydroxyl group, an optionally substituted lower alkyl group or an optionally substituted lower alkoxy group; or PA1 R.sup.1 and R.sup.2 taken together with adjacent --c.dbd.c-- form a ring; and PA1 ring A is a benzene ring which may have a substituent in addition to R.sup.1 and R.sup.2 ; or a salt thereof, PA1 24. Use of a compound of the formula: ##STR20## wherein Q is an optionally substituted carbon atom or N(O)p wherein p is 0 or 1; PA1 Y is an optionally substituted methylene group, S(O)q wherein q is an integer of 0 to 2, or an optionally substituted imino group; PA1 Z.sup.1 is a C.sub.1-3 alkylene group which may have an oxo group or a thioxo group and may contain etherified oxygen or sulfur within the carbon chain; PA1 Z.sup.2 is an optionally substituted C.sub.1-3 alkylene group; PA1 Ar is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group; PA1 one of R.sup.1 and R.sup.2 is a hydrogen atom, a halogen atom, a hydroxyl group, an optionally substituted lower alkyl group or an optionally substituted lower alkoxy group; PA1 the other is a halogen atom, a hydroxyl group, an optionally substituted lower alkyl group or an optionally substituted lower alkoxy group; or PA1 R.sup.1 and R.sup.2 taken together form a ring; and PA1 ring A is a benzene ring which may have a substituent in addition to R.sup.1 and R.sup.2 ; or a salt thereof, for the manufacture of a medicament for treating or preventing neuropathy or bone-and-joint disease, and PA1 25. A compound as described in the above item 3, which is PA1 10-(1,3-Benzodioxol-5-yl)-8,9-dihydro-7H-1,3, -benzodioxolo[4,5-f]isoindol-7-one, PA1 11-(1,3-Benzodioxol-5-yl)-7,8,9,10-tetrahydro-1,3, -benzodioxolo[4,5-g]isoquinolin-7-one, PA1 4-(1,3-Benzodioxol-5-yl)-2,3-dihydro-5-methoxy-1H-benz[f]isoindol-1-one, PA1 8,9-Dihydro-10-(4-trifluoromethylphenyl)-7H-1,3-benzodioxolo[4,5-f]isoindol -7-one, PA1 11-(1,3-Benzodioxol-5-yl)-9,10-dihydro-8H-isoindolo[5,6-f]benz[b]-1,4-dioxa n-8-one, PA1 10-(4-Fluorophenyl)-8,9, -dihydro-7H-1,3-benzodioxolo[4,5-f]isoindol-7-one, PA1 10-(1,3-Benzodioxol-5-yl)-8,9-dihydro-6-methyl-7H-1,3-benzodioxolo[4,5-f]is oindol-7-one, PA1 10-(4-Fluorophenyl)-8,9-dihydro-6-methyl-7H-1,3-benzodioxolo[4,5-f]isoindol -7-one, PA1 8,9-Dihydro-6-methyl-10-(4-trifluoromethylphenyl)-7H-1,3-benzodioxolo[4,5-f ]isoindol-7-one, PA1 10-(1,3-Benzodixol-5-yl)-8,9-dihydro-6-ethyl-7H-1,3-benzodioxolo[4,5-f]isoi ndol-7-one, 4-(1,3-Benzodioxol-5-yl)-2,3-dihydro-6-methoxy-1H-benz[f]isoindol-1-one, PA1 2,3-Dihydro-6-methoxy-4-(4-methoxypheny)-1H-benz[f]isoindol-1-one, PA1 2,3-Dihydro-6-methoxy-4-(4-trifluoromethylphenyl)-1H-benz[f]isoindol-1-one, PA1 4-(4-Fluorophenyl)-2,3-dihydro-6-methoxy-9-methyl-1H-benz[f]isoindol-1-one, PA1 4-(4-Methoxyphenyl)-2,3-dihydro-6-methoxy-9-methyl-1H-benz[f]isoindol-1-one PA1 9-(4-Fluorophenyl)-1,2-dihydro-7-methoxy-3H-pyrrolo[3,4-b]quinolin-3-one, PA1 1,2-Dihydro-7-methoxy-9-(4-methoxyphenyl)-3H-pyrrolo[3,4-b]quinolin-3-one, PA1 3,4-Dihydro-7-methoxy-5-(4-methoxyphenyl)-benzo[b][1,7]naphthyridin-1(2H)-o ne, or a salt thereof. PA1 (1) 3- to 14-membered monocyclic or fused polycyclic nonaromatic hydrocarbon groups (preferably 5- or 6-membered carbocyclic groups), for example C.sub.3-10 cycloalkene (e.g. cyclobutene, cyclopentene, cyclohexene, cycloheptene, cyclooctene, etc.) and C.sub.3-10 cycloalkane (e.g. cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, etc.). PA1 (2) 6- to 14-membered monocyclic or fused polycyclic aromatic hydrocarbon groups, for example C.sub.6-14 aryl such as phenyl, biphenyl, 1-naphthyl, 2-naphthyl, 2-indenyl, 1-anthryl, 2-anthryl, 3-anthryl, 1-phenanthryl, 2-phenanthryl, 3-phenanthryl, 4-phenanthryl, 9-phenanthryl, etc. Among them, preferred are phenyl, biphenyl, 1-naphthyl and 2-naphthyl, and phenyl is particularly preferred. PA1 (3) 5- to 10-membered monocyclic nonaromatic heterocyclic groups each containing 1 or more (e.g. 1-4, preferably 1-3) hetero atoms of one or two kinds as selected from the group consisting of nitrogen, sulfur, and oxygen in addition to carbon atoms, said heterocyclic group being optionally fused with a benzene ring, preferably 5- or 6-membered nonaromatic heterocyclic groups, more specifically monovalent groups available upon elimination of one optional hydrogen atom each from such rings as tetrahydropyridine, dihydropyridine, tetrahydropyrazine, tetrahydropyrimidine, tetrahydropyridazine, dihydropyran, dihydropyrrole, dihydroimidazole, dihydropyrazole, dihydrothiophene, dihydrofuran, dihydrothiazole, dihydroisothiazole, dihydrooxazole, dihydroisoxazole, piperidine, piperazine, hexahydropyrimidine, hexahydropyridazine, tetrahydropyran, morpholine, pyrrolidine, imidazolidine, pyrazolidine, tetrahydrothiophene, tetrahydrofuran, tetrahydrothiazole, tetrahydroisothiazole, tetrahydrooxazole, and tetrahydroisoxazole rings, preferably from 6-membered nonaromatic heterocyclic rings each containing 1 or 2 nitrogen atoms in addition to carbon (e.g. tetrahydropyridine, tetrahydropyrimidine, tetrahydropyridazine, piperidine, and piperazine rings, more preferably piperazine ring etc.). PA1 (4) 5- to 10-membered monocyclic aromatic heterocyclic groups each containing one or more (for example, 1 to 4, preferably 1 to 3) hetero atoms of one or two kinds as selected from the group consisting of nitrogen, sulfur, and oxygen in addition to carbon atoms, said heterocyclic group being optionally fused with a benzene ring, specifically monovalent groups available upon elimination of any one hydrogen atom each from aromatic heterocyclic rings such as thiophene, benzo[b]thiophene, benzo[b]furan, benzimidazole, benzoxazole, benzothiazole, benzisothiazole, naphtho[2,3-b]thiophene, thianthrene, furan, isoindolidine, xanthrene, phenoxathiin, pyrrole, imidazole, triazole, thiazole, oxazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, indole, isoindole, 1H-indazole, purine, 4H-quinolidine, isoquinoline, quinoline, phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline, carbazole, .beta.-carboline, phenanthridine, acridine, phenazine, isothiazole, phenothiazine, isoxazole, furazan, phenoxazine, isochroman, etc. (preferably pyridine, thiophene, furan, etc., more preferably pyridine) or from the fused rings available on condensation of such rings (preferably said monocyclic heterocyclic rings) with one or more (preferably 1 or 2, more preferably 1) aromatic rings (e.g. the aromatic hydrocarbons mentioned above, preferably benzene ring). PA1 a) alkyl groups [preferably lower alkyl (e.g. C.sub.1-6 alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, etc.)], PA1 b) alkenyl groups [preferably lower alkenyl (e.g. C.sub.2-6 alkenyl such as vinyl, allyl, isopropenyl, butenyl, isobutenyl, sec-butenyl, etc)], PA1 c) alkynyl groups [preferably lower alkynyl (e.g. C.sub.2-6 alkynyl such as propargyl, ethynyl, butynyl, 1-hexynyl, etc.)], PA1 d) cycloalkyl groups [preferably lower cycloalkyl (e.g. C.sub.3-6 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl optionally fused to a benzene ring which, in turn, may have 1-3 lower alkoxy groups (e.g. C.sub.1-6 alkoxy such as methoxy)], PA1 e) aryl groups (e.g. C.sub.6-14 aryl such as phenyl, biphenyl, 1-naphthyl, 2-naphthyl, 2-indenyl, [2-anthryl], 1-anthryl, 2-anthryl, 3-anthryl, 1-phenanthryl, 2-phenanthryl, 3-phenanthryl, 4-phenanthryl, 9-phenanthryl, etc., preferably phenyl), PA1 f) aralkyl groups [preferably lower aralkyl (e.g. C.sub.7-16 aralkyl such as benzyl, phenethyl, diphenylmethyl, 1-naphthylmethyl, 2-naphthylmethyl, 2-phenylethyl, 2-diphenylethyl, 1-phenylpropyl, 2-phenylpropyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, etc., more preferably benzyl)]. PA1 (1) groups of the formula ##STR21## wherein R.sup.9 and R.sup.9' may be the same or different and each represents (i) hydrogen, (ii) lower alkyl that may be halogenated, (iii) lower alkoxy that may be halogenated, (iv) lower alkylthio that may be halogenated, (v) hydroxyl, (vi) cyano, (vii) alkylcarbonyl (e.g. C.sub.1-6 alkyl-carbonyl such as acetyl, propionyl, etc.), (viii) lower alkylcarbonyloxy (e.g. C.sub.1-6 alkyl-carbonyloxy such as acetyloxy, propionyloxy, etc.), (ix) formylamino, (x) amino, (xi) mono-lower alkylamino (e.g. mono-C.sub.1-6 alkylamino such as methylamino, ethylamino, propylamino, isopropylamino, butylamino, etc.), (xii) di-lower alkylamino (e.g. di-C.sub.1-6 alkylamino such as dimethylamino, diethylamino, dipropylamino, dibutylamino, etc.), (xiii) carboxyl, (xiv) lower alkoxy-carbonyl (e.g. C.sub.1-6 alkyloxy-carbonyl such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, etc.), or (xv) lower alkyl-carbonylamino (e.g. C.sub.1-6 alkyl-carbonylamino such as acetylamino, propionylamino, etc.) wherein the "lower alkyl that may be halogenated", "lower alkoxy that may be halogenated", and "lower alkylthio that may be halogenated" include the same meaning of "lower alkyl that may be halogenated", "lower alkoxy that may be halogenated", and "lower alkylthio that may be halogenated" as mentioned for the "substituent" for the "optionally substituted carbocyclic group or optionally substituted heterocyclic group" as mentioned for Ar. R.sup.9 and R.sup.9' are the same or different and each preferably represents hydrogen, hydroxyl, cyano, C.sub.1-6 alkoxy, amino, or mono-C.sub.1-6 alkylamino, more preferably represents hydrogen, hydroxyl, amino, or mono-C.sub.1-6 alkylamino, and most preferably represents hydrogen and PA1 (2) groups of the formula &gt;C.dbd.R.sup.10 wherein R.sup.10 represents (i) ##STR22## wherein R.sup.9 and R.sup.9' are as defined above, (ii) .dbd.NR.sup.9 wherein R.sup.9 is as defined above, (iii) O or (iv) S. PA1 one of R.sup.1 and R.sup.2 is (1) a hydrogen, (2) a C.sub.1-6 alkyl, (3) a C.sub.1-6 alkoxy which may be substituted with (a) a C.sub.1-6 alkoxy-carbonyl, (b) a C.sub.7-11, aralkyl or (c) a carboxyl, or (4) a hydroxyl; PA1 the other is (1) a C.sub.1-6 alkyl, (2) a C.sub.1-6 alkoxy which may be substituted with (a) a C.sub.1-6 alkoxy-carbonyl or (b) a carboxyl, or (3) a hydroxyl. PA1 Q is (1) CR.sup.4' wherein R.sup.4' is (i) a C.sub.1-6 alkyl group which may be substituted with a di-C.sub.1-6 alkylamino group, (ii) a halogen atom, or (iii) a C.sub.1-6 alkoxy group, or (2) N; PA1 X is C.dbd.O; PA1 Y is NR.sup.5' wherein R.sup.5' is (i) a hydrogen, (ii) a C.sub.1-6 alkyl group which may be substituted with (a) a morpholino, (b) a carboxyl, (c) a C.sub.1-6 alkoxy-carbonyl, or (d) a phenyl which may be substituted with C.sub.1-6 alkoxy, or (iii) COR.sup.7" wherein R.sup.7" is (a) a hydrogen, (b) C.sub.1-6 alkyl which may be substituted with a carboxyl or a benzyloxycarbonyl, or a di-C.sub.1-6 alkylamino; PA1 m and n each represents 0; PA1 Z.sup.2 is (1) C.dbd.O, (2) CH.sub.2, (3) (CH.sub.2).sub.2, (4) (CH.sub.2).sub.3, or (5) CH--OH; PA1 Ar is (1) a phenyl group which may be substituted with (a) a halogen, (b) a C.sub.1-6 alkylenedioxy, (c) a C.sub.1-6 alkoxy which may be substituted with (c-1) a halogen or (c-2) a di-C.sub.1-6 alkylamino, or (c-3) a C.sub.1-6 alkoxy-carbonyl, (d) a C.sub.7-11 aralkyloxy, (e) C.sub.1-6 alkyl which may be substituted with a halogen, or (f) hydroxyl, (2) an optionally oxidized pyridyl group, or (i) a pyridinium group which may be substituted with C.sub.1-6 alkyl; PA1 one of R.sup.1 and R.sup.2 is (1) a hydrogen, (2) a C.sub.1-6 alkyl, (3) a C.sub.1-6 alkoxy which may be substituted with (a) a C.sub.1-6 alkoxy-carbonyl, (b) a C.sub.7-11 aralkyl or (c) a carboxyl, or (4) a hydroxyl. PA1 the other is (1) a C.sub.1-6 alkyl, (2) a C.sub.1-6 alkoxy which may be substituted with (a) a C.sub.1-6 alkoxy-carbonyl or (b) a carboxyl, or (3) a hydroxyl; PA1 R.sup.1 and R.sup.2 taken together with adjacent --c.dbd.c-- form a C.sub.1-6 alkylenedioxy group, or a C.sub.1-6 alkyleneoxy group; or PA1 ring A is a benzene ring which may have a C.sub.1-6 alkoxy group, in addition to R.sup.1 and R.sup.2 ; and a C.sub.1-6 alkoxy group or ring A and a C.sub.1-6 alkoxy group of R.sup.1 may be taken together form C.sub.1-6 alkylenedioxy group. PA1 Q is CH or N; PA1 X is C.dbd.O; PA1 m and n each represents 0; PA1 Z.sup.2 is CH.sub.2 ; and PA1 R.sup.1 and R.sup.2 taken together form a C.sub.1-6 alkylenedioxy group.
However, none of the above publications disclosing those lactone compounds (1) through (9) mention or even. suggest the excellent activities of the fused cyclic compounds of the present invention as cell differentiation inducing factors, such as bone morphogenetic protein (BMP) or neurotrophic factor (NTF), or activity of enhancing the cell differentiation inducing factor.
The foregoing suggests that compounds which enhance the activities of BMP can enhance the activities of BMP in vivo, whether endogenous or exogenous, and as such would be of value as a therapeutic agent for the above-mentioned diseases of bone. The substances reported to date as having such enhancing effects on BMP activities are retinoic acid, vitamin D3, estrogen, and glucocorticoids [V. Rosen & R. S. Thies, Trends Genet., 8, 97-102, 1992; Y. Takuwa et al., Biochem. Biophys. Res. Commun., 174, 96-101, 1991]. However, it is known that when administered, those substances promote bone resorption and/or cause such adverse reactions as hypercalcemia and ovarian cancer, and are thus not fully satisfactory as therapeutic drugs for diseases of bone.
Meanwhile, any compound capable of enhancing NTF activity should be able to enhance the activities of NTF in vivo, whether endogenous or exogenous, and be of value as a therapeutic drug for dementia and peripheral nervous disorders. As compounds enhancing activities of NGF, sabeluzole (4-(2-benzothiazolylmethylamino)-.alpha.-(p-fluorophenoxy)methyl]-1-(piper idine)ethanol) has been reported [New Current, 4, 26, 14, 1993]. However, its mechanism of action is not known and because such adverse reactions as headache, dizziness, and fatigue have been reported in clinical trials, this compound is not necessarily a suitable therapeutic drug for nerve diseases. Aside from the above, SR57746A [Neuroscience, 55, 629, 1993], T-588 [JP Kokai H4-95070], and MS430 [J. UOEN, 17, 131, 1995] are also claimed have NGF-like activity. SR57746A and T-588 are currently under clinical investigation in Alzheimer's disease but their efficacy in humans has not been established. As to MS430, its activity is suspected to be insufficient. As compounds up-regulating endogenous NGF, steroids, catechols, and cytokines have been reported [Experimental Neurology, 124, 36-42, 1993]. However, some of those compounds are neurotoxic or have pharmacologically unfavorable actions that compromise immunological potency or cause hypercalcemia, accelerated bone resorption, etc. and because no clear line of demarcation can be drawn in the state of the art between the NGF secretion inducing effect and the adverse effect on tissues other than the nervous system, those compounds are not fully satisfactory for clinical application.
Furthermore, since cell differentiation inducing factors represented by BMP and neurotrophic factors are proteins, their administration to the living body is limited. Thus, compounds which enhance the cell differentiation inducing factors, whether endogenous or exogenous, are preferably of low molecular weight.
Assuming that a compound itself has cell differentiation inducing activity which is typically possessed by BMP and neurotrophic factors, it is considered that, if its molecular weight is low, the compound can be used with greater advantage than BMP and neurotrophic factors for application to the living body as a drug for promoting bone formation and bone remodeling or a therapeutic drug for dementia and peripheral nerve diseases.
As low molecular-weight compounds known to promote the proliferation and differentiation of osteoblasts, ipriflavone [K. Notoya et al., J. Bone Miner. Res., 9, 395-400, 1994], vitamin K2 (Y. Akedo et al., Biochem. Biophys. Res. Commun., 187, 814-820, 1992], etc. are known but none of those known substances have ectopic osteoinductive activity like BMP.
As compounds having neurotrophic factor-like activities such as neurite sprouting activity and promotion of the survival of neurons lactacystin [S. Omura et al., J. Antibiot., 40, 113-117, 1991], retionic acid [M. Minana et al., Prod. Natl. Acad. Sci. USA, 87, 4335-4339, 1990], staurosporine [T. B. Shea et al., J. Neurosci. Res., 33, 398-407, 1990], K252a [G. D. Borasio et al., Neuroscience Letters, 108, 207-212, 1990], and MS818 [A. Awaya et al., Biol. Pharm. Bull., 16, 248-253, 1993], among others, are known. It is reported that above-mentioned SR57746A and MS430 have not only enhancing activity but also neurotrophic factor-like activity by themselves, too. However, as to SR57746A, among them, its efficacy in humans has not been established as pointed out above, while the other compounds are not fully satisfactory for clinical application, either, in terms of the levels of activity and toxicological risk. Therefore, there has been a real need for development of a compound having satisfactory BMP or neurotrophic activity or the corresponding agonist activity from among compounds structurally different from the above known substances.
In view of the above state of the art and for the purpose of developing a low-molecular-weight drug substance having BMP- or neurotrophic factor-like activity or the specific enhancing effect on the differentiation of osteoblasts and neurons and promotion of the survival of neurons, the inventors of the present invention explored for low molecular compounds which would exhibit cell differentiation inducing factors activity or enhancing effect on these factors. As a consequence, the inventors succeeded for the first time in the creation of a novel compound of the following formula [I], inclusive of its salt. ##STR10## wherein Q is an optionally substituted carbon atom or N(O)p wherein p is 0 or 1;